Biomedical subjects

L Lubbers

Publications and source records attributed to L Lubbers.

8 recordsLinked to original sources

PubMed2002

SKF 83959 is an antagonist of dopamine D1-like receptors in the prefrontal cortex and nucleus accumbens: a key to its antiparkinsonian effect in animals?

SKF 83959 that has a unique antiparkinson profile in animal models of Parkinson's disease is an in vitro dopamine D1 antagonist of receptors coupled to adenylyl cyclase. We hypothesized that SKF 83959, among others, interacts with dopamine D1 receptors coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. Effects of intra-accumbal injections of SKF 83959 on locomotor activity were compared to effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonist SCH 39166. Similarly to SCH 39166, SKF 83959 did not affect locomotor activity, but counteracted SKF 81297-induced locomotor activity. Effects of unilateral intra-prefrontal injections of SKF 83959 on rotational behaviour were compared to the effects of the dopamine D1 agonist SKF 81297 and the dopamine D1 antagonists SCH 23390 and SCH 39166 in rats selected on basis of their high locomotor response to novelty and pretreated with a subcutaneous injection of 0.75 mg/kg dexamphetamine. Like SCH 39166 and SCH 23390, SKF 83959 induced a bias for contralateral rotating and blocked the SKF 81297-induced bias for ipsilateral rotating. In conclusion, SKF 83959 is an in vivo antagonist of dopamine D1 receptors that are coupled to adenylyl cyclase in the nucleus accumbens and the prefrontal cortex. The role of these receptors in the antiparkinson profile of SKF 83959 is discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2002

High and low responders to novelty and mesolimbic noradrenaline: effects of noradrenergic agents on radial-maze performance.

The authors used high and low responders to novelty (HRs and LRs, respectively) to examine the effects of noradrenergic injections into the nucleus accumbens using a special radial-maze task. During the 5 successive test days, solvent-treated HRs acquired this task faster than LRs. Isoproterenol (beta-agonist) combined with phenylephrine (alpha-agonist) improved acquisition in LRs but not in HRs; this effect was counteracted by propranolol (beta-antagonist) and phentolamine (alpha-antagonist). Propranolol combined with phentolamine, as well as phentolamine alone, disrupted acquisition in HRs but not in LRs. Data show that the effects of noradrenergic agents in HRs and LRs are due to differences in acquisition directed by type-specific differences in functional mesolimbic noradrenaline.

Adrenergic alpha-Agonists↗

PubMed1999

Variation in hippocampal dynorphin b-immunoreactive mossy fiber terminal fields of apomorphine-(un)susceptible rats.

The size of distinct hippocampal sub-fields were measured in the apomorphine-susceptible and apomorphine-unsusceptible rat lines. Mossy fiber terminal fields were delineated using dynorphin B immunoreactivity and area measurements were taken from (1) the supra-pyramidal mossy fiber terminal field; (2) the intra- and infra-pyramidal mossy fiber terminal field; (3) the hilus of the fascia dentata (4) the non dynorphin B immunoreactive area of the regio inferior and fascia dentata and (5) the total area of regio inferior and fascia dentata. The data indicate that statistically significant differences in the morphometry of the hippocampal subfields of the apomorphine susceptible and unsusceptible rats are confined to the intra- and infra terminal field: the relative size of the left and right intra- and infra terminal field of apomorphine unsusceptible rats are significantly larger than those of the apomorphine susceptible rats. These data explain at least in part the differential response of these rats to novelty.

Animals↗

PubMed1999

The predictive validity of the drug-naive bilaterally MPTP-treated monkey as a model of Parkinson's disease: effects of L-DOPA and the D1 agonist SKF 82958.

The aim of this study was twofold: (1) to study the predictive validity of the drug-naive, bilaterally MPTP-treated monkey as an animal model of Parkinson's disease (PD), and (2) to investigate the therapeutic and undesired effects of the D1 agonist SKF 82958 as compared to L-DOPA treatment, in drug-naive and L-DOPA pretreated monkeys. A detailed ethogram was used, allowing the separation of therapeutic and undesired effects. Eight weeks after bilateral intracarotid MPTP administration, SKF 82958 (1 mg/kg, n = 4, SKF 82958, naive group) or methyl-L-DOPA + carbi-dopa (10 + 2.5 mg/kg, n = 4, L-DOPA group) was administered intramuscularly for 22 days. After a drug-free period of eight weeks, the L-DOPA group was treated with SKF 82958 for 22 days (SKF 82959, 1 mg/kg, n=4, pretreated). All drug treatments increased the parameters used classically to evaluate dopaminergic drugs, namely body displacement, dyskinesia and dystonia. However, the new detailed analysis revealed that L-DOPA, but not SKF 82958, had therapeutic effects, reflected by an increase in goal-directed fore-limb use. SKF 82958, but not L-DOPA, induced additional undesired effects; including epileptoid behaviours in both drug-naive and drug-pretreated monkeys. In one L-DOPA-unresponsive monkey, SKF 82958 did induce minor therapeutic effects, as well as undesired effects. Although the effects of SKF 82958 on fore-limb movements, rotational behaviours and body displacement were comparable in the naive and pretreated group, SKF 82958 re-initiated undesired effects in the L-DOPA pretreated group from day one. It is concluded that the bilaterally MPTP-treated monkey is an animal model with predictive validity for PD: it adequately predicts the therapeutic effects and undesired effects of L-DOPA. Furthermore, it is concluded that SKF 82958 is less effective than L-DOPA in the treatment of PD, because it did not induce therapeutic effects, but instead elicited several undesired effects.

Animals↗

PubMed1991

Anomalous origin of the left coronary artery from the pulmonary artery: repair by aortic reimplantation.

From 1980 to 1990, 12 patients (mean age 2.5 years, range 5 months to 9 years) with anomalous origin of the left coronary artery from the pulmonary artery were treated surgically. Five infants were operated upon in the first year of life because of persistent symptoms of congestive heart failure. In all cases, a two-coronary system was constructed by direct aortic reimplantation of the anomalous vessel with no deaths early or late over a follow-up period of up to 10 years. The technique of reimplantation was facilitated by transection of the main pulmonary artery. One patient with severe mitral regurgitation underwent, in addition, a mitral annuloplasty. A pulmonary valvotomy was performed in another patient with associated pulmonary stenosis. Three patients are receiving medication. The reimplanted anomalous left coronary artery was patent in each reevaluated patient (10/12). Left ventricular function improved considerably in all cases. Patients with symptoms should undergo repair soon after diagnosis. Direct aortic reimplantation should be technically feasible in even the smallest infant. Operative mortality is related to preoperative conditions and severity of ischemic damage of the myocardium.

Aorta↗

PubMed1981

Interfascicular nerve repair.

The technique of nerve repair that results in the greatest percentage of regeneration of axons into their original end organs will result in the greatest functional return and the best result. Of prime importance is the motor-to-motor and sensory-to-sensory axonal orientation. Anatomic and physiologic data, as well as technical expertise, must be utilized for precise nerve approximation. To this end, fascicular repair under high-power magnification is an attempt to achieve the best alignment and coaptation of the neural elements.

Axons↗

PubMedDate not supplied

Madelung deformity in skeletally immature patients: morphologic assessment using radiography, CT, and MRI.

PURPOSE: The purpose of this study was to define the pathoanatomy of the distal radius and surrounding soft tissues, identify the factors that may contribute to diminished forearm rotation, and relate these findings to alterations in wrist motion in skeletally immature patients with the Madelung deformity. METHOD: Four skeletally immature female patients with bilateral Madelung deformities (eight wrists) underwent evaluation of each wrist with radiography, CT, and MRI to assess the morphology of the deformity. Two patients (four wrists) had isolated idiopathic Madelung deformities, and two patients (four wrists) had Madelung deformities secondary to dyschondrosteosis. RESULTS: Radiographically, all wrists demonstrated dorsal bowing of the radius, marked ulnar tilting of the radius and radial tilting of the ulna, volar tilting of the distal articular surface of the radius, and triangulation of the epiphysis. On CT, patients with the idiopathic deformity demonstrated dorsal ulnar subluxation and relative supination of the carpus with respect to the distal radius. Patients with dyschondrosteosis demonstrated no ulnar subluxation and relative pronation of the carpus. All wrists demonstrated a fixed pronated deformity of the distal radius. On MRI, a physeal bar that bridged the distal metaphysis of the radius to the epiphysis was identified in all eight wrists, located on the volar aspect of the radius at the lunate facet. An anomalous volar ligament, a volar radiotriquetral ligament, and the short radiolunate ligament were hypertrophied in seven wrists. CONCLUSION: Based on its location, it is likely that a physeal bar impedes the normal development of the distal radius ulnarly. Hypertrophy of the short radiolunate ligament may be an important contributing factor to carpal pyramidalization owing to tethering on the volar pole of the lunate. Diminished forearm rotation is likely related to carpal malalignment, a fixed pronated deformity of the distal radius, and dorsal bowing of the radius.

Adolescent↗

PubMedDate not supplied

Use of high and low responders to novelty in rat studies on the role of the ventral striatum in radial maze performance: effects of intra-accumbens injections of sulpiride.

High and low responders to novelty (Wistar rats) were selected with the help of an open-field test and then equipped with intra-accumbens cannulae. They were then tested in a simple four-arm radial maze during 5 successive days, three trials per day, following intra-accumbens injections of distilled water or the dopaminergic D2 antagonist (+/-)-sulpiride. The injections were given 15 min before the first trial on each day. Both types of drug-naive rats reached the same level of performance on day 5. However, high responders made more visits, more revisits, and needed less time to make the first visit than low responders. Moreover, high responders showed their greatest increase in learning 2 days earlier than low responders. It is discussed that these differences between high and low responders are not due simply to differences in locomotor activity, but are due to a subtle, but important, difference in the mode of learning between both types. Sulpiride significantly attenuated the learning in both rat types; however, its effect in high responders was much less than that in low responders. It is suggested that the effects of sulpiride are not due to changes in locomotor activity, motivation, or perception, but are due to a learning deficit. The data are discussed in view of the genetic variation in the neurochemical and neurobiological makeup of the nucleus accumbens in both types.

Animals↗